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\begin{document}

\title{Stable and high incidence of asthma among adults in northern Sweden
during the last decades.}



\author[1]{Petri Räisänen}%
\author[1]{Helena Backman}%
\author[1]{Linnea Hedman}%
\author[1]{Martin Andersson}%
\author[1]{Caroline Stridsman}%
\author[2]{Hannu Kankaanranta}%
\author[3]{Pinja Ilmarinen}%
\author[2]{Heidi Andersen}%
\author[4]{Päivi Piirilä}%
\author[5]{Anne Lindberg}%
\author[6]{Bo Lundbäck}%
\author[1]{Eva Rönmark}%
\affil[1]{Umeå university}%
\affil[2]{Tampere University}%
\affil[3]{Seinajoki Cent Hosp}%
\affil[4]{Helsinki University Hospital}%
\affil[5]{Umeå University}%
\affil[6]{Internal Medicine/Respiratory Medicine and Allergology}%


\vspace{-1em}



  
  \date{May 22, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: The prevalence of asthma has increased both among children
and adults during the latter half of the 20th century. The prevalence
among adults is affected by the incidence of asthma in childhood but
also in adulthood. Time trends in asthma incidence are poorly studied.
The aim was to study the incidence of asthma among adults from 1996-2006
and 2006-2016, and compare the risk factor patterns. Methods: Within the
Obstructive Lung Disease in Northern Sweden (OLIN) studies, two randomly
selected population-based samples in ages 20-69 years participated in
postal questionnaire surveys about asthma in 1996 (n=7104, 85\%) and
2006 (n=6165, 77\%), respectively. A 10-year follow-up of the two
cohorts with the same validated questionnaire was performed, and n=5709
and n=4552, respectively, responded. Different definitions of population
at risk were used in the calculations of asthma incidence. The protocol
followed a study performed 1986 to 1996 in the same area. Results: The
crude incidence rate of physician-diagnosed asthma was 4.4/1000/year
(men 3.8, women 5.5) from 1996-2006, and 4.8/1000/year (men 3.7, women
6.2) from 2006-2016. When correcting for possible under-diagnosis at
study entry, the incidence rate was 2.4/1000/year from 1996-2006 and
2.6/1000/year from 2006-2016. The incidence rates were similar across
age groups. Allergic rhino-conjunctivitis was the main risk factor for
incident asthma in both observation periods (risk ratios 2.4-2.6).
Conclusions: The incidence of asthma among adults has been stable over
the last two decades, and on similar level since the 1980s. The high
incidence contributes to the increase in asthma prevalence.%
\end{abstract}%



\sloppy


\textbf{Introduction}

The prevalence of asthma is frequently studied and a consistent pattern
of a worldwide increase during the latter half of the 20th century has
been reported both among children and adults, although the increase may
have leveled off in some areas {[}1,2{]}. The reason for the increase is
unclear, but changes in lifestyle, environments, and rapid urbanization
may have contributed {[}1,3-5{]}. Prevalence is mainly a function of
incidence and remission. In adulthood, asthma is regarded as a chronic
disease due to low remission {[}6,7{]}, why the prevalence among adults
is a result of the high incidence in childhood and adolescence
{[}8-11{]} with persistence into adulthood, but also due to the
relatively high incidence in adulthood {[}4,12-24{]}. However, incidence
studies of asthma among adults are scarce, particularly population-based
studies where cohorts are followed prospectively.

Comparing incidence rates of asthma is complex as the results are highly
sensitive to the age of the study population and the methods used.
Reported incidence estimates vary substantially but are higher among
children and teenagers, 10-30/1000/year {[}8-11,20{]}, than among
adults, 0.2-5/1000/year {[}4,12-24{]}. Results from retrospective
{[}11,13,22,24,25{]} and register studies {[}13{]} tend to generate
lower incidence rates than prospective studies {[}11-21,25{]}. The
definitions of both the outcome and the population at risk significantly
influences the incidence rate {[}12,15,18,19{]}, which highlights the
importance of using the same methods and definitions to enable
comparisons of results from different studies and over time. Three
studies in Sweden or the neighboring countries, whereof one in the same
area as the current study, based on identical methods reported similar
incidence rates of physician-diagnosed asthma among adults from the
1980's up until 2006, 2-3/1000/year {[}15,16,18{]}, but it is unknown if
the incidence has changed thereafter. As the prevalence of asthma in
adults has increased in Sweden during the last decades {[}2,26{]} we
hypothesized that the incidence of asthma in adulthood still is high or
even has increased during the same period. Thus, the main aim of the
current study was to estimate the incidence of asthma among adults
during the period 1996 to 2016 by surveys of two cohorts each followed
for ten years, one from 1996 to 2006 and the other from 2006 to 2016. A
further aim was to identify risk factors for adult onset asthma.

\textbf{Material and Methods}

\textbf{Study population}

The study was performed within the Obstructive Lung Disease in Northern
Sweden (OLIN) Studies. All surveys were approved by the Regional Ethical
Review Board at Ume\selectlanguage{ngerman}å University.

The present paper is based on two random population samples, each
followed for ten years. The first sample consists of participants from a
postal questionnaire survey of a general population sample in ages 20-69
years, performed in 1996 (n=7104, 85\% response rate) {[}2{]}. This
cohort was followed up with the same questionnaire in 2006, when 5709
individuals participated (80\% response rate). The second sample was
recruited in 2006 with virtually identical methods (n=6165, 77\%
response rate) {[}2{]}, and followed up in 2016 (n=4552, 74\% response
rate). Individuals from these two cohorts that participated both at
baseline and at the follow-up after ten years constitute the study
populations in the current paper, n=5709 from cohort recruited in 1996
and n=4552 from the cohort recruited in 2006 (Table 1). The surveys were
all performed during the same time period of the year, January to May.
We have previously published incidence rates of adult-onset asthma based
on a cohort recruited in 1986 in similar ages and in the same area,
which was followed-up in 1992 {[}12{]} and 1996 {[}15{]}. The
calculations of incidence in the current paper followed the same
protocol as in these previous studies.

\textbf{Questionnaire}

The OLIN questionnaire was used in all surveys. It was originally
developed from the British Medical Research Council questionnaire and
has been validated against physiological variables {[}27{]}. It has been
used within the OLIN since 1986 and frequently in other studies of
asthma and respiratory diseases in Sweden and other countries
{[}18,19,24,26{]}.

\textbf{Definitions}

The main outcome was physician-diagnosed asthma. The definitions for
asthma and respiratory symptoms were based on the following questions:

\emph{Physician-diagnosed asthma:} ``Have you been diagnosed as having
asthma by a physician?''

\emph{Ever asthma} : ``Have you ever had asthma?''

\emph{Asthma medication use} : ``Do you currently use asthma medicines
(on a regular basis or as needed)?''

\emph{Recurrent wheeze} : ``Do you usually have wheezing or whistling in
your chest when breathing?''

\emph{Attacks of shortness of breath (SOB):} Affirmative answer to both
``Do you presently have, or have had in the last 10 years, asthma
symptoms (intermittent breathlessness or attacks of shortness of breath;
the symptoms may exist simultaneously with or without cough or
wheezing)'' and ``Have you had these problems within the last year?''

\emph{Allergic rhino-conjunctivitis (ARC)} ``Do you have or have you had
allergic nose or eye problems (hayfever)?''

\emph{Smoking habits:} Smoking habits were divided into non-smokers,
ex-smokers (quit smoking at least 12 months prior to the survey) and
smokers (smoked during the 12 months preceding the survey)

Classification of socioeconomic status was based on main occupation and
categorized into three groups; professionals, non-manual workers, and
manual workers according to classifications by Statistics Sweden.

\textbf{Statistical analyses}

The analyses were performed using the software IBM SPSS Statistics for
Windows, v26, Armonk, New York, USA. Internal missing on specific
questions in the questionnaire was low in all surveys, \textless{}5 \%.
Internal missing about asthma and respiratory symptoms was treated as a
negative response while internal missing about exposures was treated as
missing. The chi-square test was used to test for differences in
proportions and the Students t-test for differences in means. Poisson
regression analysis with physician-diagnosed asthma as outcome was
utilized to estimate risk ratios (RR) with 95\% CI. The models were
analyzed both unadjusted and adjusted with age, sex, allergic
rhino-conjunctivitis, family history of asthma, smoking habits and
socioeconomic status included as covariates.

The cumulative incidence of physician-diagnosed asthma was estimated
from two models of defining the population at risk. In model A,
individuals with any of the following variables at baseline were
excluded from the population at risk: physician-diagnosed asthma, ever
having had asthma, asthma medication use, recurrent wheeze or attacks of
SOB last 12 months. In model B, individuals were excluded from the
population at risk if reporting having physician-diagnosed asthma at
baseline. The cumulative incidence of asthma medication use and
recurrent wheeze was also estimated by model A and B, and additionally
by a third model C, where the population at risk excluded those
reporting asthma medication use at baseline when asthma medication use
was analyzed as the outcome variable, and where the population at risk
excluded those reporting recurrent wheeze at baseline when recurrent
wheeze was the outcome. As we did not have complete data on person-years
we used the cumulative incidence during the ten years observation period
in each cohort to estimate annual incidence rate by assuming the
incidence to be constant. The estimated annual incidence rate was
calculated as\(Incidence\ rate=\frac{a}{(10\times(b-\left(\frac{a}{2}\right))}\)where \emph{a} is the number of incident
cases and \emph{b} the number of subjects in the population at risk at
the start of the study, as also estimated in other studies
{[}15,18,19{]}.

\textbf{Results}

\textbf{Baseline characteristics of the cohorts}

In both cohorts the response rate was higher among women both at
baseline and at the follow-ups (Table 1). The mean age of the
individuals was 44.6 years in the cohort recruited in 1996 and 47.7
years in the cohort recruited in 2006. Smoking was more common in 1996
than 2006 (27.4\% vs. 19.3\%). Women reported significantly higher
prevalence of attacks of SOB, allergic rhino-conjunctivitis and use of
asthma medication than men in both cohorts (Table 2).

\textbf{Incidence rates}

According to model A, the incidence rate of physician-diagnosed asthma
for the period 1996 to 2006 was 2.4/1000/year (in total 108 new cases
during the ten year follow up) with minor differences between sex and
age groups. Incidence of asthma medication use was higher among women
than men (4.7/1000/year vs 3.4/1000/year, p=0.028). The incidence rate
of asthma for the period 2006 to 2016 was 2.6/1000/year (in total 93 new
cases), and higher among women than men (3.5/1000/year vs 1.7/1000/year,
p=0.001). The incidence of asthma medication use was also higher among
women than men (5.7/1000/year vs 3.3/1000/year, p=0.001) (Table 3).

According to model B, the incidence of physician-diagnosed asthma for
the period 1996 to 2006 was 4.4/1000/year (in total 225 new cases) and
the incidence of asthma medication use was 7.4/1000/year. For the period
2006 to 2016 the corresponding incidence rates were 4.8/1000/year (in
total 188 new cases) and 8.3/1000/year, respectively. These incidence
estimates were all significantly higher among women (Table 3).

According to model C, where the population at risk only excluded those
reporting the outcome variable at baseline, the incidence rates of
asthma medication use and recurrent wheeze were in between the
estimations from models A and B. The incidence of recurrent wheeze did
not differ by sex in any model or observation period (Table 3).

\textbf{Risk factors and respiratory symptoms of incident asthma}

In an adjusted Poisson regression analysis, allergic
rhino-conjunctivitis was a significant risk factor for incident
physician-diagnosed asthma, defined by model A, in both observation
periods, with RR 2.62 (1.69-4.07) and RR 2.39 (1.48-3.87), respectively
(Table 4). Female sex was a significant risk factor in the observation
period 2006 to 2016, RR 1.99 (1.22-3.25) but not from 1996 to 2006.
Family history of asthma was a borderline risk factor for the period
1996 to 2006, RR 1.50 (0.93-2.43), but significant from 2006 to 2016, RR
1.75 (1.05-2.90). Ex-smoking was a borderline risk factor from 1996 to
2006.

The same analysis as above yielded a closely similar pattern also
according to model B with family history of asthma, allergic
rhino-conjunctivitis, female sex and ex-smoking as significant risk
factors for incident physician-diagnosed asthma during the period 1996
to 2006. The same risk factors, except ex-smoking, were found for the
period 2006 to 2016 (Supplemental Table 1).

Among individuals with incident physician-diagnosed asthma in the cohort
observed from 1996 to 2006, 70\% reported attacks of SOB last 12 months,
43\% allergic rhino-conjunctivitis and 83\% used asthma medication at
the follow up in 2006. The corresponding figures for individuals with
incident physician-diagnosed asthma in the cohort observed from 2006 to
2016 were 65\%, 44\% and 80\%, respectively. None of these variables
differed significantly at follow-up between incident asthma cases in the
two cohorts.

\textbf{Discussion}

The main finding of these prospective population-based cohort studies
was that the incidence of asthma among adults in Northern Sweden was
stable from 1996 to 2016, and at similar level as from 1986 to 1996
{[}12,15{]}. Thus, the reported increase in asthma prevalence during the
last decades is not explained by an increase in asthma incidence, but by
the stable and relatively high incidence, 2-3/1000/year. The incidence
was consistently higher among women than men. In analyzes adjusted for
covariates, allergic rhino-conjunctivitis was the main risk factor for
incident asthma both 1996 to 2006 and 2006 to 2016.

To the best of our knowledge we are the first to report about trends in
asthma incidence among adults over several decades. A review article
including incidence studies from 1950s to 1990s indicated an increase in
incidence rate by time, however, the methods varied substantially
between the included studies {[}28{]}. Three longitudinal
population-based studies performed in Sweden and neighboring countries
during the 1980´s and 1990´s with almost identical methods found
incidence rates of 2-3/1000/year {[}15,16,18{]}. Our results,
2.4/1000/year from 1996 to 2006 and 2.6/1000/year from 2006 to 2016, are
in line with these studies, including the previous study in our region
(Figure 1) {[}15{]}, and indicate a continuing stable trend in incidence
rate in Sweden as a whole. However, an incidence rate of 2-3/1000/year
in combination with low remission of asthma in adulthood {[}6,7,18{]}
and similar mortality among adults with asthma as in the general
population, means about 1\% unit increase in prevalence every ten years
and thus contribute to the slowly increasing prevalence of asthma among
adults.

Only a limited number of studies about the incidence rate of asthma in
adulthood are based on prospective longitudinal population-based studies
{[}12-21,23{]}, while others are based on registers or retrospective
estimates {[}22,24{]}. These studies show considerable variation in
results, 0.7-6/1000/year due to variations in the study design including
the age of the population {[}11,13,14,25{]}, and the definitions of the
outcome and the population at risk {[}12, 14-16,18{]}. Studies ending up
with high incidence rates have often not excluded individuals with
symptoms common in asthma from the population at risk. To enable valid
comparisons between different studies it is paramount to use identical
methods.

Symptoms of asthma may occur several years before a diagnosis of asthma
is made and these symptoms may reflect undiagnosed asthma in the
population, why the incidence rate measured prospectively may be
overestimated. To reduce this bias it is reasonable to also exclude
subjects reporting symptoms of asthma from the population at risk. When
comparing different populations at risk (model A vs B) we found that the
difference in incidence rate of physician-diagnosed asthma between the
two models was much smaller in the two current cohorts under study
compared with the study from the 1980s (Figure 1). When using model B
(not correcting for possible under-diagnosis), the incidence of
physician-diagnosed asthma was 4.4-4-8/1000/year in the current cohorts,
while it was 8/1000/year in the 1980s cohort {[}12{]}. This may reflect
a decrease in under-diagnosis of asthma since the 1980s, probably due to
changed diagnostic practice and higher awareness of asthma in healthcare
and society today {[}2,26{]}. However, at the follow-up of our two
current cohorts in 2006 and 2016, individuals with incident asthma
reported similar prevalence of symptoms of asthma and use of asthma
medication. This indicate a similar disease burden among individuals
with adult onset asthma today as ten years ago, which in part
contradicts the suggested diagnostic drift regarding asthma in
healthcare. On the other hand, the major change may have occurred before
the millennium shift as a consequence of a Swedish national program
focusing on asthma during 1995, and perhaps even related to the start of
the OLIN-research program in the study area in 1986, resulting in
increased awareness of asthma in the society. Still, the higher
incidence rate of use of asthma medication compared with asthma
diagnosis may indicate some under-diagnosis of asthma also today.
However, asthma medication is also used in other respiratory diseases,
such as bronchitis and COPD, which may contribute to the high incidence.

In line with previous studies, we found that women had a higher
incidence rate of asthma compared with men {[}12-24,29,30{]} (Figure 2).
This is in contrast to children, where the incidence is higher among
boys than girls {[}8,9,11,22{]}. The reason for the sex differences is
unclear but may be related to hormonal status {[}29{]}. The obese-asthma
phenotype, often found in adult onset asthma among women {[}5,29{]}, may
be mediated by interactions between sex hormones and systemic
inflammation {[}31{]}. However, female sex has been reported to be a
predictor for persistent asthma from childhood to adulthood {[}32,33{]}
and it seems that the increasing prevalence of asthma among adults is
mainly driven by women, i.e. by lower remission rate of childhood asthma
and higher incidence rates of asthma in adult age in women than in men.

Allergic rhino-conjunctivitis is a well-known risk factor for asthma
{[}4,17,19,21{]} and is a reasonable proxy for allergic sensitization,
at least among younger and middle-aged {[}21{]}. In the current study it
was the strongest and most stable risk factor for asthma which further
strengthen the causality of the association. Several previous studies
have found smoking or ex-smoking associated with incidence of asthma
{[}4,10,12,15,19,23{]}. In the current study we found that, from 2006,
neither smoking nor ex-smoking remained as risk factors for incident
asthma among adults. This change is probably a result of the
considerable decrease in smoking that have occurred during the last two
decades in Sweden {[}2,26{]}. Not only the prevalence of smoking has
decreased but, also the number of cigarettes smoked per day has been
reduced {[}2{]}. Thus, the total level of tobacco exposure had decreased
significantly which is beneficial also for the general public health. In
contrast to previous studies which have reported several markers for low
socioeconomic status to be associated with incident asthma {[}34-36{]},
we did not find any consistent associations with socioeconomic status
based on occupation. However, though not significant, the risk ratio for
manual work was 1.75 in the 1996 cohort while the RR was close to 1 in
the most recent cohort. This may be due to improvement of the working
environment, but also due to lack of power in our study, not allowing
more detailed occupational classifications.

Several strengths support the validity of the results. First, we used
two large population-based cohorts within the same age-span and
geographical area and both cohorts were followed for ten years. Second,
the response rate was high in both cohorts, both at recruitment and
follow-up. Third, for high comparability with previous studies
{[}12,15,18{]} we used identical methods in the calculations of
incidence, and these were based on the same validated questionnaire
{[}27{]}. Furthermore, the prospective design is, compared with
retrospective studies, less associated with recall bias {[}11,25{]}.
Although the internal validity can be regarded as high, the external
validity is unclear due to the lack of studies of trends in asthma
incidence. A limitation worth noting is that despite the large sample
sizes of the cohorts and the relatively long follow-up, the study lacks
power for subgroups analyses. The studies were based on questionnaire
data which may have introduced some bias, why we cannot exclude that
some of those diagnosed as having asthma in reality had COPD. However,
the incidence were similar across all age groups. Another weakness is
the limited information about risk factors, such as body mass index and
education level, factors that have been associated with adult-onset
asthma {[}4,5,29,34{]}.

\textbf{Conclusion}

Based on identical methods, the incidence of asthma among adults was
stable from 1996 to 2016 and at almost identical level since the 1980s.
The observed high incidence in parallel with low remission in adulthood
is one explanation for the ongoing increase in prevalence of asthma
among adults. As previously found, the incidence was higher among women
than men and allergic rhino-conjunctivitis was the main risk factor.

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\textbf{Figure legends}

\textbf{Figure 1.}

Incidence rate of physician-diagnosed asthma over three decades, from
1986 to 2016, estimated by two different models of defining population
at risk.

\textbf{Footnote:}

Model A: Excluded from population at risk were those who at baseline
reported physician-diagnosed asthma, ever asthma, current use of asthma
medicine and recurrent wheeze.

Model B: Excluded from population at risk were those who reported
physician-diagnosed asthma at baseline.

*Rönmark et al. Allergy 1997 {[}12{]}

\textbf{Figure 2.}

Incidence rate of physician-diagnosed asthma by sex during three
decades, from 1986 to 2016 by sex.

\textbf{Footnote:}

Incident cases were defined by model A in all cohorts.

Model A: Excluded from population at risk were those who at baseline
reported physician-diagnosed asthma, ever asthma, current use of asthma
medicine and recurrent wheeze.

*Lundbäck et al. Resp Med 2001 {[}15{]}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\textbf{Table 1. Study population, invited and participants by age and
sex in the two cohorts followed over 10 years, by sex and among all.} &
\textbf{Table 1. Study population, invited and participants by age and
sex in the two cohorts followed over 10 years, by sex and among all.} &
\textbf{Table 1. Study population, invited and participants by age and
sex in the two cohorts followed over 10 years, by sex and among all.} &
\textbf{Table 1. Study population, invited and participants by age and
sex in the two cohorts followed over 10 years, by sex and among all.} &
\textbf{Table 1. Study population, invited and participants by age and
sex in the two cohorts followed over 10 years, by sex and among all.} &
\textbf{Table 1. Study population, invited and participants by age and
sex in the two cohorts followed over 10 years, by sex and among all.} &
\textbf{Table 1. Study population, invited and participants by age and
sex in the two cohorts followed over 10 years, by sex and among all.} &
&\tabularnewline
\midrule
\endhead
& \textbf{Cohort recruited in 1996} & \textbf{Cohort recruited in 1996}
& \textbf{Cohort recruited in 1996} & & & \textbf{Cohort recruited in
2006} & \textbf{Cohort recruited in 2006} & \textbf{Cohort recruited in
2006}\tabularnewline
& Women & Men & All & & & Women & Men & All\tabularnewline
Invited 1996, n & 3982 & 4351 & 8333 & & Invited 2006, n & 3843 & 4154 &
7997\tabularnewline
Participated (\%) & (87.2) & (83.5) & (85.3) & & Participated (\%) &
(81.6) & (72.9) & (77.1)\tabularnewline
Participated, n & 3471 & 3633 & 7104 & & Participated, n & 3135 & 3030 &
6165\tabularnewline
Invited to follow-up in 2006, n & 3336 & 3438 & 6774 & & Invited to
follow-up in 2016, n & 3001 & 2817 & 5818\tabularnewline
Participated both 1996 and 2006, n & 2876 & 2833 & 5709 & & Participated
both 2006 and 2016, n & 2389 & 2163 & 4552\tabularnewline
(\%) of participants in 1996 & (82.9) & (78.8) & (80.4) & & (\%) of
participants in 2006 & (76.2) & (71.4) & (73.8)\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2. Characteristics at recruitment; mean age and prevalence
of asthma and respiratory symptoms, smoking habits and socio-economic
group in the two cohorts, by sex and among all.}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
& \textbf{Cohort recruited in 1996 (n=5709)} & \textbf{Cohort recruited
in 1996 (n=5709)} & \textbf{Cohort recruited in 1996 (n=5709)} &
\textbf{Cohort recruited in 1996 (n=5709)} & & \textbf{Cohort recruited
in 2006 (n=4552)} & \textbf{Cohort recruited in 2006 (n=4552)} &
\textbf{Cohort recruited in 2006 (n=4552)} & \textbf{Cohort recruited in
2006 (n=4552)}\tabularnewline
& Women & Men & All & p value\textsuperscript{1} & & Women & Men & All &
p value\textsuperscript{1}\tabularnewline
Age, mean (SD) & 44.8 (13.5) & 44.4 (13.2) & 44.6 (13.3) & 0.249 & &
47.7(13.2) & 47.6 (13.1) & 47.7 (13.1) & 0.731\tabularnewline
Smoking habits, \% & & & & & & & & &\tabularnewline
Smoker & 27.7 & 23.9 & 25.8 & \textbf{\textless{}0.001} & & 20.5 & 14.2
& 17.5 & \textbf{\textless{}0.001}\tabularnewline
Ex-smoker & 19.0 & 25.0 & 22.0 & & & 23.4 & 23.9 & 23.6 &\tabularnewline
Non-smoker & 53.3 & 51.1 & 52.2 & & & 56.1 & 62.0 & 58.9
&\tabularnewline
Physician-diagnosed asthma, \% & 8.6 & 9.1 & 8.8 & 0.461 & & 12.1 & 9.9
& 11.1 & \textbf{0.016}\tabularnewline
Asthma medication, \% & 11.3 & 9.6 & 10.5 & \textbf{0.029} & & 13.5 &
10.8 & 12.2 & \textbf{0.005}\tabularnewline
Recurrent wheeze, \% & 13.2 & 12.2 & 12.7 & 0.274 & & 11.1 & 11.7 & 11.4
& 0.584\tabularnewline
Attacks of shortness of breath, \% & 15.4 & 12.5 & 13.9 & \textbf{0.002}
& & 14.1 & 11.9 & 14.3 & \textbf{0.026}\tabularnewline
Allergic rhino-conjunctivitis, \% & 24.7 & 22.2 & 23.4 & \textbf{0.029}
& & 27.4 & 22.8 & 25.2 & \textbf{\textless{}0.001}\tabularnewline
Family history of asthma, \% & 24.6 & 18.6 & 21.6 &
\textbf{\textless{}0.001} & & 25.5 & 19.8 & 22.8 &
\textbf{\textless{}0.001}\tabularnewline
Socioeconomic group, \% & & & & & & & & &\tabularnewline
Professionals & 2.8 & 7.6 & 5.3 & \textbf{\textless{}0.001} & & 5.5 &
7.7 & 6.6 & \textbf{\textless{}0.001}\tabularnewline
Non-manual workers & 43.7 & 27.8 & 35.6 & & & 47.4 & 30.1 & 39.1
&\tabularnewline
Manual workers & 53.5 & 64.6 & 59.1 & & & 47.1 & 62.1 & 54.3
&\tabularnewline
\textsuperscript{1} p-value for differences by sex & & & & & & & &
&\tabularnewline
SD=Standard deviation & SD=Standard deviation & SD=Standard deviation &
& & & & & &\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllllllllllllllllllllllllll@{}}
\toprule
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & \textbf{Table 3.
Incidence rate, n/1000/year, of different asthma variables by age group,
sex and all, by use of different definitions of population at risk.} &
\textbf{Table 3. Incidence rate, n/1000/year, of different asthma
variables by age group, sex and all, by use of different definitions of
population at risk.} & \textbf{Table 3. Incidence rate, n/1000/year, of
different asthma variables by age group, sex and all, by use of
different definitions of population at risk.} & & & &\tabularnewline
\midrule
\endhead
& & & & \textbf{Cohort followed from 1996 to 2006} & \textbf{Cohort
followed from 1996 to 2006} & \textbf{Cohort followed from 1996 to 2006}
& \textbf{Cohort followed from 1996 to 2006} & \textbf{Cohort followed
from 1996 to 2006} & \textbf{Cohort followed from 1996 to 2006} & & & &
& & & \textbf{Cohort followed from 2006 to 2016} & \textbf{Cohort
followed from 2006 to 2016} & \textbf{Cohort followed from 2006 to 2016}
& \textbf{Cohort followed from 2006 to 2016} & \textbf{Cohort followed
from 2006 to 2016} & \textbf{Cohort followed from 2006 to 2016} &
\textbf{Cohort followed from 2006 to 2016} & \textbf{Cohort followed
from 2006 to 2016} & \textbf{Cohort followed from 2006 to 2016} &
\textbf{Cohort followed from 2006 to 2016} & \textbf{Cohort followed
from 2006 to 2016} & \textbf{Cohort followed from 2006 to 2016} &
\textbf{Cohort followed from 2006 to 2016} & & & &\tabularnewline
& & & & Incidence rate, n/1000/year & Incidence rate, n/1000/year &
Incidence rate, n/1000/year & Incidence rate, n/1000/year & Incidence
rate, n/1000/year & Incidence rate, n/1000/year & & & & & & & Incidence
rate, n/1000/year & Incidence rate, n/1000/year & Incidence rate,
n/1000/year & Incidence rate, n/1000/year & Incidence rate, n/1000/year
& Incidence rate, n/1000/year & Incidence rate, n/1000/year & Incidence
rate, n/1000/year & Incidence rate, n/1000/year & Incidence rate,
n/1000/year & Incidence rate, n/1000/year & Incidence rate, n/1000/year
& Incidence rate, n/1000/year & & & &\tabularnewline
& & & & Age group & Age group & Age group & & Sex & Sex & & & p
value\textsuperscript{1} & p value\textsuperscript{1} & & & Age group &
Age group & Age group & Age group & Age group & Age group & & & Sex &
Sex & Sex & Sex & Sex & & & p value\textsuperscript{1} & p
value\textsuperscript{1}\tabularnewline
& Outcome & & & 20-39y & 40-59y & 60-69y & & W & M &
All\textsuperscript{2} & All\textsuperscript{2} & & & & & 20-39y &
20-39y & 40-59y & 40-59y & 60-69y & 60-69y & & & W & W & M &
All\textsuperscript{2} & All\textsuperscript{2} & All\textsuperscript{2}
& All\textsuperscript{2} & &\tabularnewline
Model A & Physician-diagnosed asthma & Physician-diagnosed asthma & 2.6
& 2.6 & 2.4 & 2.6 & & 2.7 & 2.2 & 2.4 & 2.4 & 0.285 & 0.285 & & & 2.8 &
2.8 & 2.6 & 2.6 & 2.5 & 2.5 & & & 3.5 & 3.5 & 1.7 & 2.6 & 2.6 & 2.6 &
2.6 & \textbf{0.001} & \textbf{0.001}\tabularnewline
& Asthma medication use & Asthma medication use & 4.4 & 4.4 & 3.9 & 3.3
& & 4.7 & 3.4 & 4.0 & 4.0 & \textbf{0.028} & \textbf{0.028} & & & 4.8 &
4.8 & 4.7 & 4.7 & 3.9 & 3.9 & & & 5.7 & 5.7 & 3.3 & 4.5 & 4.5 & 4.5 &
4.5 & \textbf{0.001} & \textbf{0.001}\tabularnewline
& Recurrent wheeze & Recurrent wheeze & 4.9 & 4.9 & 4.6 & 5.5 & & 4.5 &
5.1 & 4.8 & 4.8 & 0.396 & 0.396 & & & 4.5 & 4.5 & 5.9 & 5.9 & 4.9 & 4.9
& & & 5.3 & 5.3 & 5.2 & 5.3 & 5.3 & 5.3 & 5.3 & 0.874 &
0.874\tabularnewline
Model B & Physician-diagnosed asthma & Physician-diagnosed asthma & 4.4
& 4.4 & 4.5 & 4.1 & & 5.2 & 3.6 & 4.4 & 4.4 & \textbf{0.008} &
\textbf{0.008} & & & 4.8 & 4.8 & 4.4 & 4.4 & 5.5 & 5.5 & & & 5.8 & 5.8 &
3.6 & 4.8 & 4.8 & 4.8 & 4.8 & \textbf{0.001} &
\textbf{0.001}\tabularnewline
& Asthma medication use & Asthma medication use & 7.6 & 7.6 & 7.4 & 6.3
& & 9,0 & 5.6 & 7.3 & 7.3 & \textbf{\textless{}0.001} &
\textbf{\textless{}0.001} & & & 8.5 & 8.5 & 8.0 & 8.0 & 8.6 & 8.6 & & &
10.2 & 10.2 & 6.2 & 8.3 & 8.3 & 8.3 & 8.3 & \textbf{\textless{}0.001} &
\textbf{\textless{}0.001}\tabularnewline
& Recurrent wheeze & Recurrent wheeze & 8.2 & 8.2 & 8.9 & 10.5 & & 8.7 &
9.1 & 8.9 & 8.9 & 0.631 & 0.631 & & & 8.1 & 8.1 & 9.0 & 9.0 & 8.3 & 8.3
& & & 8.5 & 8.5 & 8.7 & 8.6 & 8.6 & 8.6 & 8.6 & 0.848 &
0.848\tabularnewline
Model C & Asthma medication use & Asthma medication use & 6.2 & 6.2 &
5.7 & 5.2 & & 7,0 & 4.6 & 5.8 & 5.8 & \textbf{\textless{}0.001} &
\textbf{\textless{}0.001} & & & 6.6 & 6.6 & 6.8 & 6.8 & 5.9 & 5.9 & & &
8.3 & 8.3 & 4.7 & 6.5 & 6.5 & 6.5 & 6.5 & \textbf{\textless{}0.001} &
\textbf{\textless{}0.001}\tabularnewline
& Recurrent wheeze & Recurrent wheeze & 6.0 & 6.0 & 6.3 & 7.9 & & 6.3 &
6.6 & 6.5 & 6.5 & 0.698 & 0.698 & & & 7.8 & 7.8 & 7.1 & 7.1 & 6.2 & 6.2
& & & 7.4 & 7.4 & 6.8 & 7.1 & 7.1 & 7.1 & 7.1 & 0.473 &
0.473\tabularnewline
Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
&\tabularnewline
Model B: Excluded from population at risk were those who reported
physician diagnosed asthma at baseline & Model B: Excluded from
population at risk were those who reported physician diagnosed asthma at
baseline & Model B: Excluded from population at risk were those who
reported physician diagnosed asthma at baseline & Model B: Excluded from
population at risk were those who reported physician diagnosed asthma at
baseline & Model B: Excluded from population at risk were those who
reported physician diagnosed asthma at baseline & Model B: Excluded from
population at risk were those who reported physician diagnosed asthma at
baseline & Model B: Excluded from population at risk were those who
reported physician diagnosed asthma at baseline & Model B: Excluded from
population at risk were those who reported physician diagnosed asthma at
baseline & Model B: Excluded from population at risk were those who
reported physician diagnosed asthma at baseline & Model B: Excluded from
population at risk were those who reported physician diagnosed asthma at
baseline & Model B: Excluded from population at risk were those who
reported physician diagnosed asthma at baseline & Model B: Excluded from
population at risk were those who reported physician diagnosed asthma at
baseline & Model B: Excluded from population at risk were those who
reported physician diagnosed asthma at baseline & Model B: Excluded from
population at risk were those who reported physician diagnosed asthma at
baseline & Model B: Excluded from population at risk were those who
reported physician diagnosed asthma at baseline & & & & & & & & & & & &
& & & & & &\tabularnewline
Model C: Excluded from population at risk were those who at baseline
reported the outcome variable & Model C: Excluded from population at
risk were those who at baseline reported the outcome variable & Model C:
Excluded from population at risk were those who at baseline reported the
outcome variable & Model C: Excluded from population at risk were those
who at baseline reported the outcome variable & Model C: Excluded from
population at risk were those who at baseline reported the outcome
variable & Model C: Excluded from population at risk were those who at
baseline reported the outcome variable & Model C: Excluded from
population at risk were those who at baseline reported the outcome
variable & Model C: Excluded from population at risk were those who at
baseline reported the outcome variable & Model C: Excluded from
population at risk were those who at baseline reported the outcome
variable & Model C: Excluded from population at risk were those who at
baseline reported the outcome variable & Model C: Excluded from
population at risk were those who at baseline reported the outcome
variable & Model C: Excluded from population at risk were those who at
baseline reported the outcome variable & Model C: Excluded from
population at risk were those who at baseline reported the outcome
variable & Model C: Excluded from population at risk were those who at
baseline reported the outcome variable & Model C: Excluded from
population at risk were those who at baseline reported the outcome
variable & & & & & & & & & & & & & & & & & &\tabularnewline
\textsuperscript{1} p-value for differences in cumulative incidence by
sex & \textsuperscript{1} p-value for differences in cumulative
incidence by sex & \textsuperscript{1} p-value for differences in
cumulative incidence by sex & \textsuperscript{1} p-value for
differences in cumulative incidence by sex & \textsuperscript{1} p-value
for differences in cumulative incidence by sex & \textsuperscript{1}
p-value for differences in cumulative incidence by sex &
\textsuperscript{1} p-value for differences in cumulative incidence by
sex & \textsuperscript{1} p-value for differences in cumulative
incidence by sex & \textsuperscript{1} p-value for differences in
cumulative incidence by sex & \textsuperscript{1} p-value for
differences in cumulative incidence by sex & \textsuperscript{1} p-value
for differences in cumulative incidence by sex & & & & & & & & & & & & &
& & & & & & & & &\tabularnewline
\textsuperscript{2} No statistical difference by study period of any of
the outcome variables were found. & \textsuperscript{2} No statistical
difference by study period of any of the outcome variables were found. &
\textsuperscript{2} No statistical difference by study period of any of
the outcome variables were found. & \textsuperscript{2} No statistical
difference by study period of any of the outcome variables were found. &
\textsuperscript{2} No statistical difference by study period of any of
the outcome variables were found. & \textsuperscript{2} No statistical
difference by study period of any of the outcome variables were found. &
\textsuperscript{2} No statistical difference by study period of any of
the outcome variables were found. & \textsuperscript{2} No statistical
difference by study period of any of the outcome variables were found. &
\textsuperscript{2} No statistical difference by study period of any of
the outcome variables were found. & \textsuperscript{2} No statistical
difference by study period of any of the outcome variables were found. &
\textsuperscript{2} No statistical difference by study period of any of
the outcome variables were found. & & & & & & & & & & & & & & & & & & &
& & &\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4. Risk factors for incident asthma defined by model A:
unadjusted and adjusted Risk Ratios with 95\% Confidence Intervals (RR,
95\%CI) from Poisson regression models.}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllllllll@{}}
\toprule
& & & \textbf{Incidence of physician-diagnosed asthma defined by model
A} & \textbf{Incidence of physician-diagnosed asthma defined by model A}
& \textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model A} &
\textbf{Incidence of physician-diagnosed asthma defined by model
A}\tabularnewline
& & & \textbf{Cohort followed from 1996 to 2006} & \textbf{Cohort
followed from 1996 to 2006} & \textbf{Cohort followed from 1996 to 2006}
& \textbf{Cohort followed from 1996 to 2006} & \textbf{Cohort followed
from 1996 to 2006} & & \textbf{Cohort followed from 2006 to 2016} &
\textbf{Cohort followed from 2006 to 2016} & \textbf{Cohort followed
from 2006 to 2016} & \textbf{Cohort followed from 2006 to 2016} &
\textbf{Cohort followed from 2006 to 2016}\tabularnewline
& & & Unadjusted & Unadjusted & & Adjusted & Adjusted & & Unadjusted &
Unadjusted & & Adjusted & Adjusted\tabularnewline
Independent variables & Category & & RR & (95\%CI) & & RR & (95\%CI) & &
RR & (95\%CI) & & RR & (95\%CI)\tabularnewline
Sex & Men & & 1 & & & 1 & & & 1 & & & 1 &\tabularnewline
& Women & & 1.23 & (0.84-1.79) & & 1.18 & (0.77-1.79) & & \textbf{2.07}
& \textbf{(1.34-3.21)} & & \textbf{1.99} &
\textbf{(1.22-3.25)}\tabularnewline
Family history of asthma & No & & 1 & & & 1 & & & 1 & & & 1
&\tabularnewline
& Yes & & \textbf{1.78} & \textbf{(1.17-2.72)} & & 1.50 & (0.93-2.43) &
& \textbf{2.10} & \textbf{(1.36-3.26)} & & \textbf{1.75} &
\textbf{(1.05-2.90)}\tabularnewline
Allergic rhino-conjunctivitis & No & & 1 & & & 1 & & & 1 & & & 1
&\tabularnewline
& Yes & & \textbf{2.47} & \textbf{(1.65-3.69)} & & \textbf{2.62} &
\textbf{(1.69-4.07)} & & \textbf{2.42} & \textbf{(1.58-3.71)} & &
\textbf{2.39} & \textbf{(1.48-3.87)}\tabularnewline
Smoking habits & Non-smokers & & 1 & & & 1 & & & 1 & & & 1
&\tabularnewline
& Ex-smokers & & \textbf{1.67} & \textbf{(1.06-2.62)} & & 1.62 &
(0.99-2.67) & & 0.87 & (0.58-1.58) & & 1.01 & (0.59-1.75)\tabularnewline
& Smokers & Smokers & 1.42 & (0.89-2.26) & & 1.38 & (0.83-2.29) & & 0.79
& (0.42-1.47) & & 0.89 & (0.46-1.69)\tabularnewline
Socioeconomic group & Professionals & & 1 & & & 1 & & & 1 & & & 1
&\tabularnewline
& Non-manual workers & Non-manual workers & 1.46 & (0.45-4.80) & & 1.32
& (0.40-4.37) & & 0.88 & (0.37-2.12) & & 0.76 &
(0.31-1.89)\tabularnewline
& Manual workers & Manual workers & 1.90 & (0.60-6.05) & & 1.75 &
(0.55-5.60) & & 0.90 & (0.38-2.12) & & 0.90 & (0.38-2.13)\tabularnewline
Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent wheeze
& Model A: Excluded from population at risk were those who at baseline
reported any of physician diagnosed asthma, ever asthma, current use of
asthma medicine and recurrent wheeze & Model A: Excluded from population
at risk were those who at baseline reported any of physician diagnosed
asthma, ever asthma, current use of asthma medicine and recurrent
wheeze\tabularnewline
The adjusted regression models included incident physician-diagnosed
asthma as outcome, and all variables presented in the table as
independent variables. Bold values indicate p\textless{}0.05. & The
adjusted regression models included incident physician-diagnosed asthma
as outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05.\tabularnewline
\bottomrule
\end{longtable}

\textbf{Supplemental Table 1. Risk factors for incident asthma, defined
by model B: unadjusted and adjusted Risk Ratios with 95\% Confidence
Intervals (RR, 95\%CI) from Poisson regression models.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllllll@{}}
\toprule
& & \textbf{Incidence of physician-diagnosed asthma defined by model B}
& \textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model B} &
\textbf{Incidence of physician-diagnosed asthma defined by model
B}\tabularnewline
& & \textbf{Cohort followed from 1996 to 2006} & \textbf{Cohort followed
from 1996 to 2006} & \textbf{Cohort followed from 1996 to 2006} &
\textbf{Cohort followed from 1996 to 2006} & \textbf{Cohort followed
from 1996 to 2006} & & \textbf{Cohort followed from 2006 to 2016} &
\textbf{Cohort followed from 2006 to 2016} & \textbf{Cohort followed
from 2006 to 2016} & \textbf{Cohort followed from 2006 to 2016} &
\textbf{Cohort followed from 2006 to 2016}\tabularnewline
& & unadjusted & unadjusted & & adjusted & adjusted & & unadjusted &
unadjusted & & adjusted & adjusted\tabularnewline
Independent variables & Category & RR & (95\%CI) & & RR & (95\%CI) & &
RR & (95\%CI) & & RR & (95\%CI)\tabularnewline
Sex & Men & 1 & & & 1 & & & 1 & & & 1 &\tabularnewline
& Women & \textbf{1.42} & \textbf{(1.09-1.85)} & & \textbf{1.35} &
\textbf{(1.01-1.81)} & & \textbf{1.60} & \textbf{(1.19-2.15)} & &
\textbf{1.55} & \textbf{(1.12-2.16)}\tabularnewline
Family history of asthma & No & 1 & & & 1 & & & 1 & & & 1
&\tabularnewline
& Yes & \textbf{2.07} & \textbf{(1.57-2.73)} & & \textbf{1.93} &
\textbf{(1.42-2.62)} & & \textbf{2.22} & \textbf{(1.65-2.99)} & &
\textbf{2.13} & \textbf{(1.53-2.97)}\tabularnewline
Allergic rhino-conjunctivitis & No & 1 & & & \textbf{1} & & & 1 & & &
\textbf{1} &\tabularnewline
& Yes & \textbf{2.79} & \textbf{(2.14-3.64)} & & \textbf{3.00} &
\textbf{(2.25-4.02)} & & \textbf{3.07} & \textbf{(2.30-4.09)} & &
\textbf{3.11} & \textbf{(2.26-4.28)}\tabularnewline
Smoking habits & Non-smokers & 1 & & & 1 & & & 1 & & & 1
&\tabularnewline
& Ex-smokers & \textbf{1.49} & \textbf{(1.08-2.05)} & & \textbf{1.42} &
\textbf{(1.01-2.01)} & & 1.13 & (0.79-1.60) & & 1.14 &
(0.78-1.67)\tabularnewline
& Smokers & 1.26 & (0.92-1.73) & & 1.12 & (0.80-1.59) & & 1.14 &
(0.78-1.68) & & 1.12 & (0.74-1.70)\tabularnewline
Socioeconomic group & Professionals & 1 & & & 1 & & & 1 & & & 1
&\tabularnewline
& Non-manual workers & 1.76 & (0.71-4.38) & & 1.53 & (0.61-3.85) & &
1.26 & (0.60-2.65) & & 1.12 & (0.53-2.35)\tabularnewline
& Manual workers & 2.29 & (0.94-5.60) & & 2.12 & (0.87-5.20) & & 1.43 &
(0.69-2.95) & & 1.38 & (0.67-2.85)\tabularnewline
Model B: Excluded from population at risk were those who at baseline
reported physician diagnosed asthma. & Model B: Excluded from population
at risk were those who at baseline reported physician diagnosed asthma.
& Model B: Excluded from population at risk were those who at baseline
reported physician diagnosed asthma. & Model B: Excluded from population
at risk were those who at baseline reported physician diagnosed asthma.
& Model B: Excluded from population at risk were those who at baseline
reported physician diagnosed asthma. & Model B: Excluded from population
at risk were those who at baseline reported physician diagnosed asthma.
& Model B: Excluded from population at risk were those who at baseline
reported physician diagnosed asthma. & Model B: Excluded from population
at risk were those who at baseline reported physician diagnosed asthma.
& Model B: Excluded from population at risk were those who at baseline
reported physician diagnosed asthma. & Model B: Excluded from population
at risk were those who at baseline reported physician diagnosed asthma.
& & &\tabularnewline
The adjusted regression models included incident physician-diagnosed
asthma as outcome, and all variables presented in the table as
independent variables. Bold values indicate p\textless{}0.05. & The
adjusted regression models included incident physician-diagnosed asthma
as outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05. & The adjusted
regression models included incident physician-diagnosed asthma as
outcome, and all variables presented in the table as independent
variables. Bold values indicate p\textless{}0.05.\tabularnewline
\bottomrule
\end{longtable}

\selectlanguage{english}
\FloatBarrier
\end{document}

